Mangiferin Stimulates Carbohydrate Oxidation and Protects Against Metabolic Disorders Induced by High-Fat Diets

Abstract

Excessive dietary fat intake causes systemic metabolic toxicity, manifested in weight gain, hyperglycemia, and insulin resistance. In addition, carbohydrate utilization as a fuel is substantially inhibited. Correction or reversal of these effects during high-fat diet (HFD) intake is of exceptional interest in light of widespread occurrence of diet-associated metabolic disorders in global human populations. Here we report that mangiferin (MGF), a natural compound (the predominant constituent of Mangifera indica extract from the plant that produces mango), protected against HFD-induced weight gain, increased aerobic mitochondrial capacity and thermogenesis, and improved glucose and insulin profiles. To obtain mechanistic insight into the basis for these effects, we determined that mice exposed to an HFD combined with MGF exhibited a substantial shift in respiratory quotient from fatty acid toward carbohydrate utilization. MGF treatment significantly increased glucose oxidation in muscle of HFD-fed mice without changing fatty acid oxidation. These results indicate that MGF redirects fuel utilization toward carbohydrates. In cultured C2C12 myotubes, MGF increased glucose and pyruvate oxidation and ATP production without affecting fatty acid oxidation, confirming in vivo and ex vivo effects. Furthermore, MGF inhibited anaerobic metabolism of pyruvate to lactate but enhanced pyruvate oxidation. A key target of MGF appears to be pyruvate dehydrogenase, determined to be activated by MGF in a variety of assays. These findings underscore the therapeutic potential of activation of carbohydrate utilization in correction of metabolic syndrome and highlight the potential of MGF to serve as a model compound that can elicit fuel-switching effects.

Consumption of a Mango Fruit Powder Protects Mice from High-Fat Induced Insulin Resistance and Hepatic Fat Accumulation

“…It has been reported that MGF may protect against hyperglycemia, hyperinsulinemia, and insulin resistance in high-fat diet-fed mice [51], in diabetic insulin-resistant rats [37], and in overweight patients [17], as well as against accelerated glucose uptake and utilization in cultured adipocytes and myotubes [51, 52]. However, MGF did not significantly affect fatty acid oxidation even under a high-fat dietary challenge [51].…”

“…However, MGF did not significantly affect fatty acid oxidation even under a high-fat dietary challenge [51]. Other major phenolic compounds found in mango fruit powder Careless TM , such as gallic acid or rutin [18], have been reported to up-regulate genes involved in lipolysis and fatty acid oxidation in adipocytes [53].…”

The Effect of Mangiferin on Improving Endothelial Dysfunction by Inhibiting Endoplasmic Reticulum Stress to Alleviate Mitochondrial Fission

“…Pasha Apontes et.al. reported that MGF can improve glucose metabolism to prevent against metabolism disorder induced by HFD, an effect that is similar to the activation of AMPK thereby ameliorating metabolism dysfunction [21]. In conclusion, the mechanism of MGF attenuating endothelial dysfunction is closely related to the activation of AMPK which inhibits ER stress.…”

“…Mangiferin (MGF) is one of the main constituents in common anemarrhena, a traditional medicine, for treating diabetes [19][20][21]. Recently, it has been reported that MGF can attenuate high-fat diet (HFD)-induced metabolism syndrome through activating AMP-actived protein Kinase (AMPK) for abnormal lipid metabolism regulation, anti-inflammation, and insulin resistance improvement [19].…”

Mitigation of Insulin Resistance by Mangiferin in a Rat Model of Fructose-Induced Metabolic Syndrome Is Associated with Modulation of CD36 Redistribution in the Skeletal Muscle

“…Mangiferin and the related herbs have been demonstrated to have antidiabetic activity in rodents (Ichiki et al, 1998;Li et al, 2004;Li et al, 2008;Muruganandan et al, 2005;Akase et al, 2011;Apontes et al, 2014;Han et al, 2015). Furthermore, it has been recently reported that mangiferin supplementation improves insulin resistance index in overweight patients (Na et al, 2015).…”